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L0301P53 - Resting Membrane Potential and Action Potential
Biological Function of Electricity *sense the environment **light, pressure, temperature, chemical *need to be turned into electricity **fast and discrete signalling *problems with electrical signalling in the body may lead to: **mutations - epilepsy, long QT syndrome, cystic fibrosis **disease - cerebral palsy, multiple sclerosis, kidney disease **drugs - off-target side effects Electrical Potential in Cells *all cells have an electrical potential *can vary between different types of cells **skeletal muscle, heart ventricle: ~-90mV **neurons: ~-60-80mV **generally ranges from -30 to -90mV *due to different ion concentrations inside and outside the cell **inside the cell ***potassium (K+): chaperone proteins ***proteins - generally negative **outside the cell ***sodium (Na+) ***chloride (Cl-) The Cell - Ion Concentrations *different ionic concentrations inside and outside the cell **permits cells to be different, independent **creates a Nernst potential for each ion *same “density” (osmolarity) of total ions inside and outside the cell *the difference in charge of the ions dictates the membrane potential (V) Nernst Equation *used to calculate the exact equilibrium potential in mV *takes into consideration external and internal ion concentrations, temperature, ratio of concentrations *when Xo = Xi, then Ex = 0mV **∴need concentration difference to get a potential difference *Nernst potential also called the “equilibrium potential” or “reversal potential” *for each ion: Distribution of Ions *Arises due to: 1. Lipophilic nature of the cell membrane *plasma membrane: hydrophobic *∴hydrophilic ions cannot pass through 2. Ion Pumps/Transporters *transmembrane proteins that use ATP to move ions against their [ ] gradients *establish and maintain ionic differences, and ∴, the resting membrane potential *very costly in terms of energy 3. Semipermeability of the Cell Membrane *at rest, K+ channels open while Na+ channels are mostly closed **not much movement of K+ due to attraction to proteins 4. Ion Channels *permeability routes for ions and water *open to allow ions to move through freely down its concentration gradient *inactivation gate may be present *fast and free - no use of energy Ion Pumps/Transporters Characteristics Ion Channels Characteristics Goldman-Hodgkin-Katz Equation *accounts for the difference between V calculated by addition of Nernst potentials and the actual resting V **difference arises due to the fact there is a steady leak of Na+ into the cell (chloride is reversed as it is a negative ion) *Vm - membrane potential *o = outside and i = inside concentrations *p = permeability **determined by number of ion channels open where pK defined as =1. pNa, pCl etc all relative to pK At rest: *pK defined as = 1 as it is most dominant **∴ Vm closest to Nernst for K *pNa calculated in terms of fraction of pK **0.01 at rest in neurons During activity: *channels open = large increase in pNa *Vm is now a combination of Nernst of K and Nernst of Na Summary Membrane Potential *electricity is created by differences in ion concentrations inside and outside the cell **established by ion channels that are variously open/closed **maintained by transporters Process *when ion channels open **low resistance ® *ions move across the membrane (in or out) **increase current (I) *causes change in membrane potential **��Vm Ion Channels *activation **change in membrane potential ***most significantly: depolarisation *conductance **conformational change **hydration shell lost **ion binds within pore (1 or more sites) **ion moves through the channel pore ***into or out of the cell *characteristics **state: closed, open, inactivated **gates: selectivity, inactivation *channelopathies **mutation or dysfunction of ion channels **cause of diseases like epilepsy, sudden cardiac death, cystic fibrosis etc